The objectives of this proposal are to: elucidate the mechanisms by which estrogens regulate growth, DNA synthesis and mitosis in the rat uterus; determine what other nonestrogenic hormones are required for this process to occur normally; determine how antiestrogens such as nafoxidine affect the uterus directly and how they affect the uterine response to estrogens; and determine how pesticides such as DDT affect the uterus directly and how they affect the uterine response to estrogens. Studies in the first area will focus on how estrogens regulate cellular growth, DNA replication and mitosis, and correlate each of these specific events ith estrogen-receptor binding to nuclear acceptor sites. These studies will examine individual uterine cell types utilizing histological techniques to monitor DNA synthesis and mitosis. Attempts will be made to determine if unique classes of nuclear acceptor sites regulate different phases of the overall uterine response. The propose studies are also aimed at determining the mechanisms by which thyroid hormones affect uterine DNA synthesis and cell division in response to estrogens; to determine if thyroid hormones are required in both mature and immature rats for a normal uterine response to estrogen; and to determine if the effect of thyroid hormone is a direct effect on the uterus, or if a second site of action is involved. Additional studies will also be performed to determined how antiestrogens such as nafoxidine and pesticides such as DDT affect each specific phase of the uterine response themselves, and also, how they affect the tissue response to estradiol. These studies will monitor the effect of antiestrogens and DDT on the different uterine cell types present in the immature rat uterus.